Diagnostic imaging in modern dental practice still relies mainly on visual inspection or x-ray radiography, a technology that remains largely unchanged since the late 1800s. The early detection of small caries and the evaluation of microscopic enamel cracks prior to facture are two major issues that may be addressed with the application of 3-D optical imaging techniques. Optical coherence tomography (OCT), an optical imaging technology that measures light reflections to form a 3-D image in much the same way that ultrasound measures sound reflections, is attractive for dental imaging because it permits the evaluation of microscopic tissue morphology at m-scale resolutions without the need for ionizing radiation or exogenous contrast. OCT is not yet ready for general use in dental practice, however, as it suffers from several technical constraints such as shallow imaging depth, slow speed, and the lack of practical commercial probes designed specifically for dental use. In this Phase I proposal, Diagnostic Photonics (DxP) will demonstrate that the technical innovations brought about by interferometric synthetic aperture microscopy (ISAM), the next-generation technology built on OCT, will overcome key shortcomings that have prevented the adoption of 3-D optical imaging technology in dental practice to date. We will perform ISAM imaging of ex vivo dental specimens with an existing DxP handheld ISAM probe system, quantitatively evaluate the performance improvement over conventional OCT, develop improved ISAM algorithms and optical configurations for extreme depth-of-field dental imaging, and design a dedicated intraoral probe for use in Phase II. In future Phase II work, the dedicated handheld dental probe will be constructed and tested in an in vivo clinical investigation. Clinical studies will include the evaluation of diagnostic accuracy and repeatability of caries identification, differentiation between active and inactive caries, enamel crack identification, and crack size measurement. These studies will also evaluate the reliability of the system and reproducibility of the results. The clinical, engineering, and business experts at DxP have a demonstrated track record of successfully implementing innovative medical imaging technologies and introducing them into clinical practice. This track record, when combined with the enabling technology of ISAM, yields a significant new opportunity to improve dental care through technical innovation.